Higher plane of nutrition pre-weaning enhances Holstein calf mammary gland development through alterations in the parenchyma and fat pad transcriptome

Vailati-Riboni, M.; Bucktrout, R. E.; Zhan, S.; Geiger, A.; McCann, J. C.; Akers, R. M.; Loor, J. J.

doi:10.1186/s12864-018-5303-8

Table 3 IPA-predicted up-stream regulators in mammary parenchyma (PAR) of Holstein heifer calves (n = 6/treatment) fed pre-weaning (week 1 to 8 of life) an enhanced (EH) (1.08 kg of powder/calf/day, 28.9% crude protein, 26.2% fat, DM basis) or restricted (R; represents the industry standard or control) milk replacer (0.44 kg of powder/head/day, 20.9% crude protein, 19.8% fat, DM basis)

From: Higher plane of nutrition pre-weaning enhances Holstein calf mammary gland development through alterations in the parenchyma and fat pad transcriptome

Upstream Regulator	Fold Change	Molecule Type	Predicted State	Z-score	P-value	Target molecules in dataset
arachidonic acid		chemical - endogenous mammalian	Activated	2.177	0.0185	AQP3,EGFR,EPHB1,HMOX1,SLC2A4
hyaluronic acid		chemical - endogenous mammalian	Activated	2.176	0.0406	CXCL10,MMP2,NCF2,PTHLH,SERPINE1
sphingosine-1-phosphate		chemical - endogenous mammalian	Activated	2.219	0.0141	ANGPT1,CXCL10,EGFR,HAS2,SERPINE1
tretinoin		chemical - endogenous mammalian	Activated	2.45	0.000000758	ABHD2,ALDH1A3,APBB1IP,APLN,B3GALT5,BPI,BRCA1,CCND2,CCNE1,CCR1,CSF3R,CXCL10,CYP1A1,DAPK2,DHRS9,EGFR,FABP5,FOLR2,GFAP,GJA1,GPR21,HAS2,HEY2,HMOX1,HOXD1,HSD17B11,LIPA,MAFB,MAPK10,MMP19,MSC,MSI1,MTHFD2,NCF2,NEFH,PLEK,PLP1,POSTN,PTGIS,PTHLH,RAI14,SEMA5B,SERPINE1,SLC2A4,STRA6,Stra6l,STRA8,TP73,TRPC4,ZP2
CD3		complex	Inhibited	−2.605	0.0126	AQP3,C2,CCND2,CCNE1,CCR1,CD5,CD8B,CDC25A,CXCL10,EEF1A2,EPHB1,IL15RA,MAF,MMP2,MTHFD2,PLEK,TFEC,TFPI2,TP73
LDL		complex	Activated	2.175	0.0475	CXCL10,HAS2,HMOX1,IL1RN,MMP2,MSC,RYR2,SERPINE1
NFkB (complex)		complex	Activated	2.378	0.000618	ADAMTS9,ALDH1A3,CCND2,CXCL10,CXCL5,CXCL9,DBP,DIO1,EGFR,FABP5,GFAP,HAS2,HMOX1,IL15RA,IL1RN,MMP2,NCF2,NR1D1,SERPINE1,SLC2A4,TFEC,TFPI2
Pdgf (complex)		complex	Activated	2.36	0.0000339	CCND2,EGFR,GJA1,HEY2,HMOX1,MEOX2,MMP2,PIK3R3,SERPINE1
PDGF BB		complex	Activated	2.851	0.000116	ACAT2,BRCA1,CCNE1,CNN1,EGFR,FBLN5,FOXC2,FOXS1,GDA,GJA1,HMOX1,MMP2,MYH11,POSTN,SERPINE1,VCAN
PI3K (complex)		complex	Activated	3.227	0.0000982	ADAM12,APLN,CCND2,CCNE1,CCR1,CXCL10,FABP5,GJA1,HMOX1,IL1RN,MMP2,MTHFD2,PLA2G5,POSTN,SERPINE1
Pka		complex	Activated	2.213	0.0267	CXCL10,GJA1,HAS2,HMOX1,PTHLH,SLC1A3
CSF2		cytokine	Activated	2.644	0.0101	ACE,BUB1B,CCR1,CXCL10,ERCC6L,FIGNL1,FOLR2,HAS2,IL1RN,MME,MMP2,NLRP3,POLE,TARP,UBD
CSF3	1.023	cytokine	Activated	2.393	0.000635	CCND2,CCNE1,CSF3R,CXCL5,GFAP,GJA1,HMOX1,IL1RN,LYZ,MMP2
EDN1	−1.29	cytokine	Activated	2.599	0.0021	ADAM12,ADAM19,APLN,CDC25A,EGFR,GJA1,MMP2,RAMP3,SERPINE1,VCAN
IFNG		cytokine	Activated	2.381	0.0000278	ACOD1,ADORA1,ALDH1A3,C2,CALB2,CCND2,CCR1,CXCL10,CXCL9,DBP,DIO1,FABP5,FAM107A,FCN1,GFAP,GJA1,GPR146,HAS2,HCK,HMOX1,IL15RA,IL1RN,MMP2,NCF2,NDRG4,NLRP3,NR1D1,NTF4,PIGR,PLA2G5,PLEK,PTHLH,SERPINE1,SLC11A1,SLC1A3,SLC6A1,SYNM,TMOD1,TP73,TREM2,TRPC4,UBD
IL1A		cytokine	Activated	2.794	0.0123	ALDH1A3,CXCL10,CXCL5,CYP1A1,HMOX1,IL1R2,IL1RN,MMP2,SERPINE1
IL1B	1.404	cytokine	Activated	2.1	0.00000379	ACOD1,ANGPT1,CCR1,CXCL10,CXCL5,CXCL9,CYP1A1,DBP,DIO1,FABP5,GJA1,HAS2,HMOX1,IL15RA,IL1R2,IL1RN,LHB,MAPT,MMP2,MYH11,NR1D1,PIGR,PLA2G5,POSTN,PTGIS,PTHLH,SEMA3A,SERPINE1,SLC1A3,SLC2A4,TFPI2,TREM2,UBD,VCAN
IL27		cytokine	Activated	2.747	0.00154	CCND2,CXCL10,CXCL9,HPGD,IL15RA,IL1RN,MAF,UBD
IL4		cytokine	Activated	2.113	0.00411	ADAM19,CCND2,CCNE1,CD5,CSF3R,CXCL10,CXCL9,GJA1,HCK,HPGD,IL15RA,IL1R2,IL1RN,MAF,MAFB,MAL,MMP2,PIGR,PLOD2,POSTN,PTHLH,SERPINE1,TFEC,TREM2
SPP1	1.148	cytokine	Activated	2.724	0.0000515	ANGPT1,BRCA1,CCNE1,CDC25A,CXCL5,EGFR,GFAP,HAS2,HMOX1,MMP2,S100A4,SERPINE1
TNF	1.151	cytokine	Activated	3.185	0.00000109	ACE,ACOD1,ADAMTS7,ADORA1,ALDH1A3,ANGPT1,APLN,AQP3,BMPER,BUB1B,CCND2,CCR1,CD5,CDH11,CNN1,CXCL10,CXCL5,CXCL9,CYP1A1,DIO1,EGFR,ENTPD5,FABP5,FOXC2,GFAP,GJA1,HMOX1,HPGD,IL15RA,IL1R2,IL1RN,MEOX2,MMP2,MSC,NCF2,NEFH,NLRP3,PDE2A,PER2,PIGR,PLA2G5,PLOD2,PLP1,POSTN,PPP1R3C,PTHLH,SERPINE1,SLC11A1,SLC1A3,SLC2A4,SORBS1,TFPI2,TREM2,UBD,WISP1
TNFSF12	−1.07	cytokine	Activated	2.163	0.0193	ADAM12,CCR1,CXCL10,IL1R2,SLC2A4
Akt		group	Activated	2.521	0.000711	ANGPT1,AQP3,BRCA1,CCND2,CXCL10,EGFR,HMOX1,HPGD,MMP2,SERPINE1,SLC2A4,VCAN
Alpha catenin		group	Inhibited	−2.433	0.0159	ADAMTS12,CDH11,CXCL10,LYZ,MMP19,MMP2
ERK		group	Activated	2.636	0.000184	CCNE1,CCR1,CXCL10,CYP1A1,EGFR,HEY2,HMOX1,MAFB,MAL,MMP2,SERPINE1,STMN4,VCAN
ERK1/2		group	Activated	3.053	0.000325	APLN,BRCA1,CCND2,CDC25A,CXCL10,CXCL5,GJA1,HAS2,HPGD,MMP2,POSTN,SERPINE1,VCAN,WISP1
IL1		group	Activated	2.622	0.0000596	C2,CXCL10,CXCL5,CXCL9,CYP1A1,DDC,EGFR,GFAP,GJA1,HMOX1,IL1R2,IL1RN,LYZ,MMP2,PIGR,SERPINE1,VCAN
Jnk		group	Activated	2.211	0.00202	APLN,BRCA1,CCNE1,GJA1,HMOX1,LHB,MMP2,POSTN,SERPINE1,VCAN
Mek		group	Activated	2.602	0.0164	CCND2,CXCL10,CXCL9,GDA,HAS2,LHB,SERPINE1,SLC16A6
Nr1h		group	Inhibited	−2.183	0.000167	ACE,AQP3,C2,CCND2,CXCL10,HCK,MPZ,NLRP3,SLC2A4,TRPC4
P38 MAPK		group	Activated	2.164	0.00109	ANGPT1,CCND2,CCNE1,CXCL10,CXCL9,CYP1A1,DDC,GJA1,HMOX1,IL1RN,MAL,MMP2,MYH11,POSTN,SERPINE1
Tnf (family)		group	Activated	2.416	0.0341	CXCL10,CXCL9,CYP1A1,GJA1,HTR2A,SERPINE1
AGT		growth factor	Activated	2.57	0.00000192	ACAT2,ACE,ADAM12,ANGPT1,APLN,BRCA1,CCND2,CCNE1,CDC25A,CXCL10,EGFR,FOXP2,GJA1,HAS2,HMOX1,MAPT,MMP2,NCF2,POSTN,PPP1R3C,PTHLH,SCN2A,SERPINE1
ANGPT2	−1.107	growth factor	Activated	2.17	0.00155	ADAM12,ASPHD1,EGFR,HMOX1,MAPK10,MAPK12,MMP2,POSTN,PTHLH,SERPINE1
EGF		growth factor	Activated	2.738	0.00000409	ANGPT1,AQP3,BRCA1,CCND2,CCNE1,CDH11,CXCL5,CYP1A1,E2F3,EGFR,GFAP,GJA1,HAS2,HMOX1,HPGD,IL1R2,MMP2,PLAGL1,PTHLH,S100A4,SERPINE1,SLC2A4,TFPI2,VCAN
FGF2	−1.127	growth factor	Activated	2.287	0.000375	ACE,ANGPT1,AQP3,CCND2,CDC25A,CDH11,EGFR,GFAP,GJA1,HAS2,MAPT,MEOX2,MMP2,MPZ,S100A4,SERPINE1
INHA	1.185	growth factor	Inhibited	−2.067	0.0000109	CCND2,CCNE1,CNN1,EGFR,HAS2,HSD17B11,MMP2,MYH11,SERPINE1,WISP1
JAG2	−1.135	growth factor	Inhibited	−2	0.00417	CCR1,CXCL5,CXCL9,IL1RN
NRG1	−1.228	growth factor	Activated	2.252	0.0351	ANGPT1,BRCA1,CCND2,CCNE1,GDA,HMOX1,PYGM,SLC2A4
TGFB1	1.118	growth factor	Activated	2.435	1.64E-09	ACE,ACKR1,ADAM12,ADAM19,ADAMTS12,ADORA1,ANGPT1,APLN,BUB1B,C2,CALB2,CCND2,CCNE1,CCR1,CDC25A,CDH11,CLCA2,CNN1,COL11A1,CPXM1,CRHR2,CRMP1,CXCL10,FABP5,FAM107A,FBLN5,FCER1A,FOXC2,GFAP,GJA1,GPR146,GPR21,HAS2,HMOX1,HOXD1,HPGD,IL1RN,KCNMB1,MAF,MMP2,MPZ,MTHFD2,MYH11,NCF2,NDRG4,NLRP3,PLAGL1,PLOD2,PLXNC1,POSTN,PPP1R3C,PRKCG,PTHLH,S100A4,SEMA3A,SERPINE1,TENM4,TP73,USH1C,VCAN,WISP1,XPNPEP2
TGFB2	1.073	growth factor	Activated	2.184	0.000322	CDH11,CNN1,HAS2,HMOX1,PLOD2,PTHLH,SERPINE1,VCAN
AKT1	−1.008	kinase	Activated	2.424	0.0000153	ACAT2,CCND2,CCNE1,CXCL10,DLX3,FABP5,HMOX1,LAMA1,LIPA,MMP2,MYH11,PLP1,RAMP3,SERPINE1,VCAN
AR		ligand-dependent nuclear receptor	Activated	2.362	0.0000416	AQP3,BUB1B,CA4,CDH11,EGFR,FABP5,GFAP,GJA1,LMOD1,MME,MSI1,MTHFD2,NTF4,PIGR,Pln,PLOD2,PTHLH,SERPINE1,TARP,VCAN
miR-16-5p (and other miRNAs w/seed AGCAGCA)		mature microrna	Inhibited	−2.185	0.021	CCND2,CCNE1,CDC25A,CHEK1,E2F3,EGFR,HMOX1,PLAG1
mir-155		microrna	Inhibited	−2.213	0.00404	CXCL10,EGFR,HMOX1,MAF,MME,SERPINE1
CAMP	4.064	other	Activated	2.22	0.0141	CSF3R,CXCL10,CXCL5,IL1R2,IL1RN
RETNLB		other	Activated	2	0.0417	CCR1,LAMA1,MMP2,WISP1
EGR1	−1.092	transcription regulator	Activated	2.217	0.000185	ACE,CCND2,CCR1,EGFR,ENPEP,HMOX1,HPGD,LHB,LYZ,SERPINE1,TP73
FOXM1	1.769	transcription regulator	Activated	2.405	0.0136	BUB1B,CCND2,CCNE1,CDC25A,MMP2,VCAN
MYC	1.009	transcription regulator	Activated	2.887	0.00135	ACOD1,ANGPT1,BMPER,BRCA1,BUB1B,CCND2,CCNE1,CDC25A,CHEK1,CNTNAP2,CXCL10,DLX3,E2F3,FABP5,FBLN5,FBN2,FXYD1,GJA1,HAS2,HMOX1,KLK6,LYZ,NTF4,PCDH18,PLP1,PNCK,SCAMP5,SERPINE1,SLC11A1,TP73,WISP1
NFKB1	−1.113	transcription regulator	Activated	2.369	0.00876	ADORA1,CCND2,CRMP1,CXCL10,CXCL9,EGFR,GJA1,HAS2,HMOX1,IL1RN
NOTCH1	1.053	transcription regulator	Activated	2.14	0.00536	ADAM19,ANGPT1,CCND2,CCNE1,EGFR,GFAP,HEY2,MMP2,MPZ,SERPINE1
SMAD2	1.071	transcription regulator	Activated	2.219	0.0128	HAS2,HMOX1,MMP2,PTHLH,SERPINE1
SMAD3	1.052	transcription regulator	Activated	2.184	0.0134	ADORA1,CCND2,CCNE1,CXCL10,HAS2,HMOX1,LHB,PTHLH,SERPINE1
SP1	1.148	transcription regulator	Activated	2.178	0.000139	ABHD2,CCND2,CXCL10,CXCL5,DLX3,EGFR,FOLR2,GJA1,HAS2,HMOX1,LAMA1,LHB,LIPA,MEOX2,MMP2,MYH11,NCF2,NTF4,SERPINE1,SLC11A1,TFPI2,TP73
SRF	−1.107	transcription regulator	Inhibited	−2.186	0.0248	CNN1,CPM,FCN1,GDA,LMOD1,MAPK10,MAT1A,MYH11,PDE2A,RAI2,SEMA3A
TLR2	1.392	transmembrane receptor	Activated	2.013	0.0183	CCR1,CXCL10,GJA1,HMOX1,IL15RA,IL1RN,LHB
TLR3	1.088	transmembrane receptor	Activated	2.183	0.0227	ACOD1,CPM,CXCL10,HMOX1,IL1R2,IL1RN,LIPA,PIK3R3,SERPINE1

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